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The Pathobiology of Periodontal Diseases May Affect Systemic Diseases: Inversion of a Paradigm
Abstract
A new paradigm for the pathobiology of periodontitis is presented, and the manner in which periodontitis may relate to susceptibility for certain systemic diseases such as cardiovascular disease and preterm labor is described. Periodontitis is caused by a small group of Gram‐negative bacteria present on the tooth root surfaces as biofilms. Lipopolysaccharide (LPS) and other substances gain access to the gingival tissues, initiate and perpetuate immunoinflammation, resulting in production of high levels of proinflammatory cytokines. These induce production of matrix metalloproteinases which destroy the connective tissues of the gingiva and periodontal ligament, and prostaglandins which mediate alveolar bone destruction. Periodontitis may enhance susceptibility to systemic diseases in several ways. LPS and viable Gram‐negative bacteria from the biofilms and proinflammatory cytokines from the inflamed periodontal tissues may enter the circulation in pathogenic quantities. In addition, periodontitis and certain systemic diseases, such as cardiovascular disease, share risk factors including tobacco smoking, male gender, race/ethnicity, stress, and aging. Ann Periodontol 1998;3:108–120.
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“Periodontal disease shares many associative and causative links with systemic disease, and it increases susceptibility to systemic diseases via shared risk factors, such as by harboring pathogenic gram‐negative anaerobes in subgingival biofilms, and by fashioning the periodontium as a reservoir for pro‐inflammatory mediators.199”
From The oral microbiome: Role of key organisms and complex networks in oral health and disease (2021) · cites this paper as [199]
In the citing paper
“Periodontal disease predisposes humans to cardiovascular pathologies, such as atherosclerosis and myocardial infarction, as a result of inducing increased levels of systemic pro‐inflammatory cytokines, inflammatory cells and infiltrates, and white blood cell counts.199”
From The oral microbiome: Role of key organisms and complex networks in oral health and disease (2021) · cites this paper as [199]
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Takamisawa, K., Sugita, N., Komatsu, S., Wakasugi, M., Yokoseki, A., Yoshihara, A., Kobayashi, T., Nakamura, K., Onodera, O., Momotsu, T., et al. (2020) · Heliyon · doi:10.1016/j.heliyon.2020.e05531 · Cited by 7
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Disciplina Protezare Totală, F. D. M. D., Bicheru, M. M., Preoteasa, C. T., Disciplina Ergonomie şi Metodologia Cercetării Ştiinţifice, F. D. M. D., Imre, M. M., Disciplina Protezare Totală, F. D. M. D., Preoteasa, E. S., & Disciplina Protezare Totală, F. D. M. D. (2018) · Romanian Journal of Stomatology · doi:10.37897/rjs.2018.4.2 · Cited by 2
Das, N. (2020) · Perio J · doi:10.26810/perioj.2020.a3 · Cited by 2
Planning and Implementation of Oral Health Services for Older Adults in India: The Immediate Need
Talwar, M. (2023) · Springer eBooks · doi:10.1007/978-981-16-1914-4_191-1 · Cited by 2
Non-Alcoholic Fatty Liver and Periodontal Disease: Is there a Relationship? A Contemporary Review
Hatipoğlu, H. (2024) · Journal of Inonu Liver Transplantation Institute · doi:10.14744/jilti.2023.10820 · Cited by 2
“[29] The concept of focal infection should be mentioned hereby.”
BackgroundDurgapal, S., & Mamatha, S. V. (2025) · Indian Journal of Dental Research · doi:10.4103/ijdr.ijdr_715_23 · Cited by 2
Doença periodontal e obesidade: existe alguma relação?
Bertolini, P. F. R., Filho, O. B., Pomílio, A., & Alves, P. E. V. (2012) · Revista de Ciências Médicas · doi:10.24220/2318-0897v19n1/6a830 · Cited by 2
Metaloproteinasas de matriz en enfermedades del tracto gastrointestinal
Medina, C., Santana, A., Quintero, E., Radomski, M. W., & Guarner, F. (2004) · Gastroenterología y Hepatología · doi:10.1016/s0210-5705(03)70509-3 · Cited by 2
Subantimicrobial Dose Doxycycline — Host Modulation in the Treatment of Periodontitis
Zahavi, T., & Caton, J. G. (2005) · Cited by 2
Ganesh, P. (2015) · International Journal of Dental Science and Research · doi:10.1016/j.ijdsr.2015.11.005 · Cited by 2
ASSOCIATION BETWEEN PERIODONTAL PATHOGENS AND CORONARY ARTERY DISEASE: A CASE-CONTROL STUDY
Reza, T. A. M., Soboti, F., Alireza, A. G., Dehaki, M. G., Shariati, M., & Kazemi, B. (2011) · Cited by 2
Rosa, W. D., Camargo, A. C. C., Buono, E. A. D., & Neto, L. B. (2017) · Revista de Odontologia da Universidade Cidade de São Paulo · doi:10.26843/ro_unicid.v21i3.457 · Cited by 2
The Effects Of Emotional Stress On Periodontal Disease
ALTINTEPE, D. S. S., & DEVELİOĞLU, D. D. H. (2012) · DergiPark (Istanbul University) · Cited by 2
Ren, J., Ding, Y., Yu, H., Zhou, Y., & Yu, W. (2018) · Biomedical Research - India · doi:10.4066/biomedicalresearch.29-17-3173 · Cited by 2
“gingivalis can enter gingival tissues and elicit an inflammatory response leading to an increase in pro-inflammatory cytokines [25].”
BackgroundPeriodontal Disease and Systemic Health
Ide, M. (2021) · BDJ clinician's guides · doi:10.1007/978-3-030-76243-8_3 · Cited by 2
Periodontal Disease and the Cardiovascular System
Diseases, H. O. I. (2005) · Kluwer Academic Publishers eBooks · doi:10.1007/0-306-47926-5_6 · Cited by 2
Inanc, M., & Cengiz, K. (2011) · InTech eBooks · doi:10.5772/23166 · Cited by 2
Kaur, K., Vaziri, S., Romero‐Reyes, M., Paranjpe, A., & Jewett, A. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10040875 · Cited by 2
“IL-1β and TNF-α can also induce the endothelial cells in the blood vessels to express higher ICAM-1 (CD54) and other adhesion molecules [20], allowing more leukocytes to migrate into the periodontal tissues.”
BackgroundGibson, G., & Niessen, L. C. (2006) · Springer eBooks · doi:10.1007/0-387-22621-4_62 · Cited by 2
ANXIETY, EXHAUSTION AND DEPRESSION IN RELATION TO PERIODONTAL DISEASES
Johannsen, A. (2006) · Figshare · Cited by 2
(2012) · Wiley eBooks · doi:10.1002/9781118480045.ch9 · Cited by 2
Neuroinflammation: The link between periodontal disease and Alzheimer’s disease
Zisis, V., Zisis, S., Andreadis, D., & Athanasios, P. (2022) · International Journal of Applied Dental Sciences · doi:10.22271/oral.2022.v8.i1f.1455 · Cited by 1
Modern approach to the identification and elimination of periodontal infection
Atanasovska-Stojanovska, A. (2012) · Macedonian Journal of Medical Sciences (University of Skopje) · doi:10.3889/mjms.1857-5773.2012.0228 · Cited by 1
“mk atherosclerosis, stroke, osteoporosis, premature birth and low-birth-weight babies; and by increasing the damage caused by diabetes mellitus and chronic respiratory diseases [2].”
BackgroundAssociation between psychosocial factors and periodontitis
Juma, S. S. S. (2011) · Journal of Baghdad College of Dentistry · Cited by 1
Metadata
- Authors
- Page, R. C.
- Affiliations
- University of Washington (US)
- Corresponding author
- Page, Roy C.
- Venue
- Annals of Periodontology
- Publisher
- Wiley
- Published
- 1998-07
- Volume
- 3
- Issue
- 1
- Pages
- 108-120
- ISSN
- 1553-0841 (ISSN-L)
- 2162-5131
- OpenAlex
- W1967814211
- Cited by
- 420
- References
- 45
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 16 · 2023: 8 · 2022: 17 · 2021: 20 · 2020: 14 · 2019: 16 · 2018: 12 · 2017: 18 · 2016: 12 · 2015: 18 · 2014: 18 · 2013: 26 · 2012: 34
- FWCI
- 19.34
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Periodontology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5p01de008555-10)
- National Institute of Dental and Craniofacial Research (T32 DE 07063, P30 DE09743, P01DE08555, T32DE007063, P30DE009743)
- Topics
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Health Sciences › Dentistry › Periodontics › Periodontal Regeneration and Treatments
- Health Sciences › Dentistry › General Dentistry › Dental Research and COVID-19
- Keywords
- periodontitis, cardiovascular disease, preterm labor, Gram-negative bacteria, biofilm, lipopolysaccharide, immune inflammation, inflammatory cytokines, matrix metalloproteinases, prostaglandins, alveolar bone loss, periodontal ligament, risk factors, smoking
- MeSH terms
- Animals, Cardiovascular Diseases, Disease Susceptibility, Focal Infection, Dental, Gram-Negative Anaerobic Bacteria, Health Status, Humans, Periodontitis, Risk Factors, Cytokines, Biofilms, Inflammation Mediators
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